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Abstract We present a nation-wide network analysis of non-fatal opioid-involved overdose journeys in the United States. Leveraging a unique proprietary dataset of Emergency Medical Services incidents, we construct a journey-to-overdose geospatial network capturing nearly half a million opioid-involved overdose events spanning 2018–2023. We analyze the structure and sociological profiles of the nodes, which are counties or their equivalents, characterize the distribution of overdose journey lengths, and investigate changes in the journey network between 2018 and 2023. Our findings include that authority and hub nodes identified by the HITS algorithm tend to be located in urban areas and involved in overdose journeys with particularly long geographical distances.

Abstract Background Endogeneous and exogeneous sex hormones can impact the frequency and severity of migraine attacks, but the underlying mechanisms are poorly understood. In this study, we investigate the relationship between female sex hormones and Pituitary Adenylate Cyclase-Activating Polypeptide-38 (PACAP-38) concentrations in plasma of women with migraine and healthy controls, aiming to elucidate potential hormonal influences on PACAP dynamics and their relevance to migraine pathophysiology. Methods This analysis is part of a cross-sectional, matched-cohort study. We recruited two groups of women with episodic migraine: one with a regular menstrual cycle (M-RMC) and another undergoing combined oral contraceptive treatment (M-COC). Additionally, we included corresponding age-matched control groups without migraine for both categories (C-RMC and C-COC). For participants with a RMC, the study visits were scheduled during the perimenstrual period (menstrual cycle day 2 ± 2) and periovulatory period (day 13 ± 2). Participants using COC were examined at day 4 ± 2 of the hormone-free interval and between day 7–14 of the hormone intake phase. During these visits, PACAP-38 concentrations in plasma were measured using a commercial Enzyme-linked-immunosorbent assay (ELISA) kit. Results The study included 120 women, with 30 participants in each group. Women with migraine and a RMC had significantly higher PACAP-38 plasma concentrations compared to healthy controls at both study visits [day 2 ± 2: M-RMC: 2547.41 pg/ml (IQR 814.27 – 4473.48) vs. C-RMC: 1129.49 pg/ml (IQR 257.34 – 2684.88), p = 0.025; day 13 ± 2: M-RMC: 3098.89 pg/ml (IQR 1186.29 – 4379.47) vs. C-RMC: 1626.89 (IQR 383.83 – 3038.36), p = 0.028]. In contrast, PACAP-38 levels were comparable between migraine and control groups receiving COC. Women with migraine and a RMC exhibited higher PACAP-38 concentrations during menstruation compared to those using COC during the hormone-free interval. Conclusion Systemic PACAP-38 concentrations in women vary based on the presence of migraine diagnosis and their hormonal status.

The IR absorption mapping of two multiblock copolymers based on poly(ethylene glycol) and poly(ε-caprolactone) segments (PEG-b-PCL) in poly(acid lactic) and poly(ε-caprolactone) blends (PLA/PCL) was performed via AFM nanoscale IR spectroscopy. These copolymers, having the same number average molar masses (Mn‾) but varying block sizes, were added into the blend in different amounts (1 and 5 wt%) using a co-rotating twin-screw extrusion. The results revealed that copolymers with smaller blocks are preferentially located near the interface when incorporated in small quantities. Increasing the copolymer content led to preferential diffusion into the PLA matrix. Compatibilization with the longer block-size copolymers also led to preferential diffusion in the PLA matrix, albeit with a tendency to form micelles. This hampers the overall mechanical properties of the blend, making the compatibilized blend more brittle than neat PLA. Compatibilization with the short block-size copolymers showed no micellization and improved the mechanical behavior of PLA/PCL.

Abstract Previous studies of DNA sequence and karyotypic data have revealed high genetic diversity in the Physalaemus cuvieri – Physalaemus ephippifer species complex—a group of small leptodactylid frogs in South America. To date, seven major genetic lineages have been recognized in this group, with species delimitation tests supporting four to seven of them as valid species. Among these, only P. ephippifer shows heteromorphic sex chromosomes, but the implications of cytogenetic divergence for the evolution of this group are unknown. We analyzed karyotypic, mitochondrial DNA, and 3RAD genomic data to characterize a putative contact zone between P. ephippifer and P. cuvieri Lineage 1, finding evidence for admixture and karyotypic evolution. We also describe preliminary evidence for admixture between two other members of this species complex—Lineage 1 and Lineage 3 of P. cuvieri. Our study sheds new light on evolutionary relationships in the P. cuvieri – P. ephippifer species complex, suggesting an important role of karyotypic divergence in its evolutionary history and underscoring the importance of hybridization as a mechanism of sex chromosome evolution in amphibians.

Background: Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used in therapy due to their anti-inflammatory and analgesic properties. However, their clinical use is often associated with gastrointestinal complications. Thus, this study aimed to investigate the protective effect of a sulfated iota-carrageenan isolated from the marine alga Solieria filiformis (IC-Sf) against naproxen-induced gastrointestinal injury. Methods: Parameters of gastrointestinal injury, secretory and motor functions, and toxicity were evaluated. Results: The results demonstrated that IC-Sf significantly reduced naproxen-induced gastrointestinal macroscopic injury, with a maximum effect observed at 30 mg/kg. IC-Sf also preserved gastrointestinal antioxidant defense and prevented lipid peroxidation, with a reduction in the non-protein sulfhydryl group (NP-SH) and malondialdehyde (MDA) concentrations induced by naproxen. Additionally, IC-Sf mitigated naproxen-induced gastrointestinal inflammation, as evidenced by reduced myeloperoxidase (MPO) activity, tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1β). IC-Sf did not alter gastric secretion or gastrointestinal motility. In addition, the animals treated with IC-Sf did not present toxic effects. Conclusions: In conclusion, IC-Sf protected the gastrointestinal tract against the harmful effects of naproxen by inhibiting the inflammatory response and lipid peroxidation, suggesting its potential as a new therapeutic agent or food additive.

One of the sources of sustainable energy with great, still untapped potential is wind power. One way to harness such potential is to develop technology for offshore use, more specifically at high depths with floating turbines. It is always critical that their structural designs guarantee that their natural frequencies of vibration do not match the frequencies of the most important oscillatory loads to which they will be subjected. This avoids resonance and its excessive undesired oscillatory responses. Based on that, a 3D finite element model of a 15 MW semi-submersible floating offshore wind turbine was developed in the commercial software ANSYS Mechanical ® to study its dynamic behavior and contribute to the in-depth analysis of structural modeling of FOWTs. A tower and floating platform were individually modeled and coupled together. The natural frequencies and modes of vibration of the coupled system and of its components were obtained by modal analysis, not only to verify the resonance, but also to investigate the determinant factors affecting such behaviors, which are not extensively discussed in literature. It was found that there is strong coupling between the components and that the tower affects the system as a result of its stiffness, and the floater as a result of its rotational inertia. The platform’s inertia comes mainly from the ballast and the effects of added mass, which was considered to be a literal increase in mass and was modeled in two manners: first, it was approximately calculated and distributed along the submerged flexible platform members and then as a nodal inertial element with the floater being considered as a rigid body. The second approach allowed an iterative analysis for non-zero frequencies of vibration, which showed that a first approximation with an infinite period is sufficiently accurate. Furthermore, the effects of the mooring lines was studied based on a linear model, which showed that they do not affect the boundary conditions at the bottom of the tower in a significant way.

Abstract Background People with physical disabilities and/or chronic diseases tend to have an inactive lifestyle. Monitoring physical activity levels is important to provide insight on how much and what types of activities people with physical disabilities and/or chronic diseases engage in. This information can be used as input for interventions to promote a physically active lifestyle. Therefore, valid and reliable physical activity measurement instruments are needed. This scoping review aims 1) to provide a critical mapping of the existing literature and 2) directions for future research on measurement properties of device-based instruments assessing physical activity behavior in ambulant adults with physical disabilities and/or chronic diseases. Methods Four databases (MEDLINE, CINAHL, Web of Science, Embase) were systematically searched from 2015 to April 16th 2023 for articles investigating measurement properties of device-based instruments assessing physical activity in ambulatory adults with physical disabilities and/or chronic diseases. For the majority, screening and selection of eligible studies were done in duplicate. Extracted data were publication data, study data, study population, device, studied measurement properties and study outcome. Data were synthesized per device. Results One hundred three of 21566 Studies were included. 55 Consumer-grade and 23 research-grade devices were studied on measurement properties, using 14 different physical activity outcomes, in 23 different physical disabilities and/or chronic diseases. ActiGraph (n = 28) and Fitbit (n = 39) devices were most frequently studied. Steps (n = 68) was the most common used physical activity outcome. 97 studies determined validity, 11 studies reliability and 6 studies responsiveness. Conclusion This scoping review shows a large variability in research on measurement properties of device-based instruments in ambulatory adults with physical disabilities and/or chronic diseases. The variability highlights a need for standardization of and consensus on research in this field. The review provides directions for future research.

Covering: 2019 to 2023. Even with the advent of modern and complementary spectroscopy techniques, comprehensive characterization of natural product continues to represent an onerous and time-consuming task, being far away to become rather “routine”. Mainly due to their highly complex structures and small amount of isolated sample, in milligram or sub-milligram quantities, structural misassignment of natural products are still a recurrence theme in the modern literature. Since the seminal paper from Nicolau and Snider, in 2005, evaluating the various cases of reassignment of natural products, from the present era, in which NMR parameters calculations play such an important role in the structural elucidation of natural products, helping to uncover and ultimately revise the structure of previously reported compounds, a pertinent question arises: are we still chasing molecules that were never there? In this minireview, we intent to discuss the current state of computational NMR parameter calculations, with a particular focus on their application in the structural determination of natural products. Additionally, we have conducted a comprehensive survey of the literature spanning the years 2019–2023, in order to select and discuss recent noteworthy cases of incorrectly assigned structures that were revised through NMR calculations. Therefore, our main goal is to show what can be done through computational simulations of NMR parameters, currently user-friendly and easily implemented by non-expert users with basic skills in computational chemistry, before venturing into complex and time-consuming total synthesis projects. In conclusion, we anticipate a promising future for NMR parameter calculations, fueled by the ongoing development of user-friendly tools and the integration of artificial intelligence. The emergence of these advancements is poised to broaden the applications of NMR simulations, offering a more accessible and reliable means to address the persistent challenge of structural misassignments in natural product chemistry.

Endometrial and cervical cancer are among the most frequently diagnosed malignancies globally. Nitric oxide receptor-soluble guanylyl cyclase (sGC) is a heterodimeric enzyme composed of two subunits, α1 and β1. Previously we showed that sGCα1 subunit promotes cell survival, proliferation, and migration, but the role of sGCβ1 subunit has not been addressed. The aim of the present work was to study the impact of sGCβ1 restoration in proliferation, survival, migration, and cell signaling in endometrial and cervical cancer cells. We found that sGCβ1 transcript levels are reduced in endometrial and cervical tumors vs normal tissues. We confirmed nuclear enrichment of sGCβ1, unlike sGCα1. Overexpression of sGCβ1 reduced cell viability and augmented apoptotic index. Cell migration and invasion were also negatively affected. All these sGCβ1-driven effects were independent of sGC enzymatic activity. sGCβ1 reduced the expression of epithelial-to-mesenchymal transition factors such as N-cadherin and β-catenin and increased the expression of E-cadherin. sGCβ1 impacted signaling in endometrial and cervical cancer cells through significant downregulation of Akt pathway affecting some of its main targets such as GSK-3β and c-Raf. Our results show for the first time that sGCβ1 exerts several antiproliferative actions in ECC-1 and HeLa cell lines by targeting key regulatory pathways.

Seven new abietane diterpenoids, comprising medusanthol A–G (1–3, 5, 7–9) and two previously identified analogs (4 and 6), were isolated from the hexane extract of the aerial parts of Medusantha martiusii. The structures of the compounds were elucidated by HRESIMS, 1D/2D NMR spectroscopic data, IR spectroscopy, NMR calculations with DP4+ probability analysis, and ECD calculations. The anti-neuroinflammatory potential of compounds 1–7 was evaluated by determining their ability to inhibit the production of nitric oxide (NO) and the proinflammatory cytokine TNF-α in BV2 microglia stimulated with LPS and IFN-γ. Compounds 1–4 and 7 exhibited decreased NO levels at a concentration of 12.5 µM. Compound 1 demonstrated strong activity with an IC50 of 3.12 µM, and compound 2 had an IC50 of 15.53 µM; both compounds effectively reduced NO levels compared to the positive control quercetin (IC50 11.8 µM). Additionally, both compounds significantly decreased TNF-α levels, indicating their potential as promising anti-neuroinflammatory agents.

Abstract The current study focuses on the investigation of AVPR2 (VTR2C) protein-coupled receptor variants specific to different primate taxa. AVPR2 is activated by the neurohormone AVP, which modulates physiological processes, including water homeostasis. Our findings reveal positive selection at three AVPR2 sites at positions 190, 250, and 346. Variation at position 250 is associated with human Congenital Nephrogenic Diabetes Insipidus (cNDI), a condition characterized by excessive water loss. Other 13 functional sites with potential adaptive relevance include positions 185, 202, 204, and 252 associated with cNDI. We identified SH3-binding motifs in AVPR2’s ICL3 and N-terminus domains, with some losses observed in clades of Cercopithecidae, Callitrichinae, and Atelidae. SH3-binding motifs are crucial in regulating cellular physiology, indicating that the differences may be adaptive. Co-evolution was found between AVPR2 residues and those in the AVP signal peptide/Neurophysin-2 and AQP2, other molecules in the same signaling cascade. No significant correlation was found between these Primates’ taxon-specific variants and the bioclimatic variables of the areas where they live. Distinct co-evolving amino acid sequences in functional sites were found in Platyrrhini and Catarrhini, which may have adaptive implications involving glucocorticoid hormones, suggesting varied selective pressures. Further studies are required to confirm these results.

Abstract Background Clinical trials and real-world studies revealed a spectrum of response to CGRP(-receptor) monoclonal antibodies (mAbs) in migraine prophylaxis, ranging from no effect at all to total migraine freedom. In this study, we aimed to compare clinical characteristics between super-responders (SR) and non-responders (NR) to CGRP(-receptor) mAbs. Methods We performed a retrospective cohort study at the Headache Center, Charité – Universitätsmedizin Berlin. The definition of super-response was a ≥ 75% reduction in monthly headache days (MHD) in the third month after treatment initiation compared to the month prior to treatment begin (baseline). Non-response was defined as ≤ 25% reduction in MHD after three months of treatment with a CGRP-receptor mAb and subsequent three months of treatment with CGRP mAb, or vice versa. We collected demographic data, migraine disease characteristics, migraine symptoms during the attacks in both study groups (SR/NR) as well as the general medical history. SR and NR were compared using Chi-square test for categorical variables, and t-test for continuous variables. Results Between November 2018 and June 2022, n = 260 patients with migraine received preventive treatment with CGRP(-receptor) mAbs and provided complete headache documentation for the baseline phase and the third treatment month. Among those, we identified n = 29 SR (11%) and n = 26 NR (10%). SR reported more often especially vomiting (SR n = 12/25, 48% vs. NR n = 4/22, 18%; p = 0.031) and typical migraine characteristics such as unilateral localization, pulsating character, photophobia and nausea. A subjective good response to triptans was significantly higher in SR (n = 26/29, 90%) than in NR (n = 15/25, 60%, p = 0.010). NR suffered more frequently from chronic migraine (NR n = 24/26, 92% vs. SR n = 15/29, 52%; p = 0.001), medication overuse headache (NR n = 14/24, 58% versus SR n = 8/29, 28%; p = 0.024), and concomitant depression (NR n = 17/26, 65% vs. SR n = 8/29, 28%; p = 0.005). Conclusion Several clinical parameters differ between SR and NR to prophylactic CGRP(-R) mAbs. A thorough clinical evaluation prior to treatment initiation might help to achieve a more personalized management in patients with migraine.

Abstract Background Patients with sarcopenia have a higher risk of poor recovery after coronary artery bypass grafting (CABG). Little is known about the impact of changes in muscle strength (the primary indicator for sarcopenia) on health-related quality of life (HR-QoL). This study aimed to (1) identify subgroups with different muscle strength trajectories, (2) identify differences in preoperative risk factors among trajectory group membership, and (3) explore their prognostic value on postoperative HR-QoL in patients undergoing CABG. Methods In this prospective observational study 131 patients undergoing elective CABG completed grip strength tests and HR-QoL questionnaires. Latent Class Growth Mixture Modelling (LCGMM) was used to identify clinically relevant trajectories (> 5% of study population) for weight-normalised grip strength, measured at admission, 3 days, and 6 months after surgery. Differences between trajectory group membership at baseline were evaluated. The impact of trajectory group membership on postoperative HR-QoL was evaluated with multiple linear regression models. Results Due to low numbers (n = 15), female patients were excluded from LCGMM and subsequent statistical analyses. In males (n = 116), we identified two main weight-normalised grip strength trajectories: a “stable average” trajectory with a slight decline immediately post-surgery and recovery to preoperative levels (n = 85) and a “high” trajectory with a considerable immediate decline after surgery but followed towards a higher level of recovery compared to preoperative level (n = 27). The “stable average” patients were older (68 vs. 57 years; P = 0.003), had more diabetes (27% vs. 4%; P = 0.01) and had a higher BMI (27.8 vs. 24.8; P = 0.005) compared to the “high” group. After correction for age, diabetes, and baseline HR-QoL, group trajectory membership was not associated with postoperative HR-QoL, yet an increase in individual change scores of weight-normalised grip strength was associated with a better postoperative HR-QoL. We also identified one small trajectory group (n = 4, ≤ 5%). Conclusions This study showed two relevant weight-normalised grip strength trajectories in male patients undergoing CABG, varying in important preoperative risk factors. While change scores of grip strength per weight did predict postoperative HR-QoL, the trajectory subgroups could not predict postoperative HR-QoL. Future research should focus on female patients, reacting potentially different on CABG and/or rehabilitation treatment. Trial registration NCT03774342, 12-12-2018.

Electric induction motors are the type of motor most commonly operated in industry, and for this reason technologies that predict faults and reduce the corrective maintenance are of great interest. In this context, this paper presents a predictive maintenance tool of electric motors using the concepts of Digital Twin (DT) and Industrial Internet of Things (IIoT). The proposed system is innovative, as it monitors the motor current and temperature by means of sensors and a low-cost acquisition module, and these measurements are sent via Wi-Fi to a database. The concept of DT was leveraged by providing the measurements as inputs to a high-fidelity strongly-coupled model of the monitored monitor, using the Finite Element Method (FEM). The results obtained are satisfactory, because the sensors used presented acceptable errors that do not interfere with the reliability of the results. The computer simulation showed relative errors below 4% in the conductivity analysis and 10% in the temperature analysis. In addition, the simulation allows verifying the internal temperature of the motor, its resistive losses, and the intensity of the magnetic flux at each pole. It is worth pointing out that the internal analysis performed is only possible due to the combination of IIoT and computer simulations. Therefore, they allow a better diagnosis of the motor’s operational status and also a time estimate for the next maintenance service, thus being ideal for the industrial sector.

The Great Horned Owl (Bubo virginianus) inhabits myriad habitats throughout the Americas and shows complex patterns of individual and geographic morphological variation. The owl family Strigidae is known to follow ecogeographic rules, such as Gloger’s rule. Although untested at the species level, these ecogeographic rules may affect B. virginianus plumage coloration and body size. Previous studies have indicated that, despite this species’ morphological variability, little genetic differentiation exists across parts of their range. This study uses reduced representation genome-wide nuclear and complete mitochondrial DNA sequence data to assess range-wide relationships among B. virginianus populations and the disputed species status of B. v. magellanicus (Magellanic or Lesser Horned Owl) of the central and southern Andes. We found shallow phylogenetic relationships generally structured latitudinally to the north of the central Andes, and a deep divergence between a southern and northern clade close to the Marañón Valley in the central Andes, a common biogeographic barrier. We identify evidence of gene flow between B. v. magellanicus and other subspecies based on mitonuclear discordance and F-branch statistics. Overall differences in morphology, plumage coloration, voice, and genomic divergence support species status for B. v. magellanicus.

Abstract Background Hand-rim wheelchair propulsion is straining and mechanically inefficient, often leading to upper limb complaints. Previous push–pull lever propulsion mechanisms have shown to perform better or equal in efficiency and physiological strain. Propulsion biomechanics have not been evaluated thus far. A novel push–pull central-lever propulsion mechanism is compared to conventional hand-rim wheelchair propulsion, using both physiological and biomechanical outcomes under low-intensity steady-state conditions on a motor driven treadmill. Methods In this 5 day (distributed over a maximum of 21 days) between-group experiment, 30 able-bodied novices performed 60 min (5 × 3 × 4 min) of practice in either the push–pull central lever wheelchair (n = 15) or the hand-rim wheelchair (n = 15). At the first and final sessions cardiopulmonary strain, propulsion kinematics and force production were determined in both instrumented propulsion mechanisms. Repeated measures ANOVA evaluated between (propulsion mechanism type), within (over practice) and interaction effects. Results Over practice, both groups significantly improved on all outcome measures. After practice the peak forces during the push and pull phase of lever propulsion were considerably lower compared to those in the handrim push phase (42 ± 10 & 46 ± 10 vs 63 ± 21N). Concomitantly, energy expenditure was found to be lower as well (263 ± 45 vs 298 ± 59W), on the other hand gross mechanical efficiency (6.4 ± 1.5 vs 5.9 ± 1.3%), heart-rate (97 ± 10 vs 98 ± 10 bpm) and perceived exertion (9 ± 2 vs 10 ± 1) were not significantly different between modes. Conclusion The current study shows the potential benefits of the newly designed push–pull central-lever propulsion mechanism over regular hand rim wheelchair propulsion. The much lower forces and energy expenditure might help to reduce the strain on the upper extremities and thus prevent the development of overuse injury. This proof of concept in a controlled laboratory experiment warrants continued experimental research in wheelchair-users during daily life.

Abstract Background Although knee extensors are essential in daily activities (e.g. walking, climbing stairs), knee extensor strength is often not measured in clinical settings. Existing devices to test muscle strength are not always suitable to accurately measure the high forces of this muscle group. Therefore, a device to test muscle strength that is convenient, feasible, reliable, and valid in clinical settings is required. This study evaluated the reliability, responsiveness, and level of discomfort of the newly developed Q-Force ӀӀ (i.e. a portable device to measure isometric knee extensor strength) in healthy middle-aged and elderly adults. Methods Participants (n = 22) conducted two standardized test sessions on the Q-Force ӀӀ (five to ten days apart). Each session consisted of one familiarisation trial followed by three trials of peak isometric knee extension per each leg. Per trial, peak and mean knee extension force (N) and torque (Nm) were measured at 90° flexion. The level of discomfort was determined using a visual analog scale (VAS: 0-100). Intra Class Correlation (ICC, model: two-way mixed with absolute agreement), Standard Error of Measurement (SEM), and minimal detectable change (MDC) were determined. A repeated measures ANOVA was used to determine between-test variation. Results Excellent test-retest (ICC > 0.95) and inter-trial (ICC > 0.91) reliability for both legs were shown. No significant differences were found in peak and mean knee forces and torques between test and retest of both legs, indicating good test-retest reliability (P-value range: 0.360-0.538; F(1,21) range: 0.4-0.9). The SEM of the peak and mean forces and torques ranged from 28.0 to 30.4 N (6.0-6.8%) and from 9.2 to 10.4 Nm (6.4-7.7%), respectively. The MDC for these outcomes ranged respectively from 77.6 to 84.1 N (16.5-18.8%) and from 25.5 to 28.9 Nm (17.6-21.4%). The level of discomfort was low (median range: 7-10, IQR: 4-18). Conclusion The portable Q-Force ӀӀ is a comfortable, responsive, and relatively cheap device with excellent test-retest reliability. This device would be potentially suitable to measure isometric knee extensor strength in clinical settings.

Non-native species can have profound implications on the survival of native ones. This is especially true for some invasive crabs, such as the green crab Carcinus maenas, a native species to the Northern Hemisphere that has been introduced into southern Argentina, from where it could expand through Argentina, Chile, and the Antarctic Peninsula. Hence, there is interest in forecasting changes in C. maenas habitat suitability through time to predict if potential future invasions might occur. Here, by using a Species Distribution Model (SDM) approach, we estimated the habitat suitability for C. maenas along southern South America and the Antarctic Peninsula under two future climate-change scenarios. Our results reveal that under current conditions, habitat suitability for C. maenas along the Antarctic Peninsula is null and very restricted in Argentina and Chile. Habitat suitability along the Antarctic Peninsula remained null in the short-term (30 years) and long-term future (80 years), despite the climate-change scenario considered. Surprisingly, when considering future conditions, habitat suitability along the coast of Argentina and Chile decreased and became nil for some currently occupied locations. Thus, the SDM results suggest that climate change could have a negative effect on the habitat suitability of C. maenas leading to potential local extinctions.

ABSTRACT The thermal and luminous conditions in aviaries affect the production and quality of eggs. Thus, the aim of the present study was to evaluate the thermal and luminous environment of commercial laying hen aviaries equipped with compact fluorescent (CF) and light-emitting diode (LED) lamps and their influence on egg production and quality. The study was carried out in two commercial laying hen facilities with similar construction features and management. The first facility was illuminated with CF lamps and the second with LED lamps. The thermal environment was assessed via air temperature, air relative humidity, and enthalpy. The evaluated lamps provided a similar thermal environment in both facilities. The aviary equipped with LED lamps showed higher illuminance than the one equipped with a CF lamp. Production performance was evaluated through feed intake (FI), feed conversion (FC), mortality (M), and laying percentage (LP). Specific gravity (SG) was used to evaluate eggshell quality. The variables related to production performance and eggshell quality of laying hens raised in aviaries equipped with LED lamps were statistically equal (F-test, p > 0.05) to those raised in aviaries equipped with CF lamps. These results indicate that the replacement of CF lamps with LED lamps does not adversely affect the yield and quality of eggs.

Wheelchair tennis players are prone to develop shoulder injuries, due to the combination of wheelchair propulsion, overhead activities and daily wheelchair activities. A methodical literature search was conducted to identify articles on shoulder complaints in wheelchair tennis, wheelchair sports and tennis. The aims were to identify (1) type of shoulder complaints; (2) possible risk factors for the development of shoulder injuries; (3) musculoskeletal adaptations in the shoulder joint in wheelchair tennis players. Fifteen papers were included in this review, five on wheelchair tennis, three on wheelchair sports and seven on tennis. Type of shoulder complaints were acromioclavicular pathology, osteoarthritic changes, joint effusion and rotator cuff tears. Possible risk factors for the development of shoulder injuries in wheelchair tennis are overhead movements, repetitive activation of the anterior muscle chain and internal rotators, as well as a higher spinal cord injury level. Muscular imbalance with higher values for the internal rotators, increase in external range of motion, decrease in internal range of motion and reduced total arc of motion were the most common proposed musculoskeletal adaptations due to an unbalanced load. These presented risk factors and musculoskeletal adaptations might help researchers, coaches and wheelchair tennis players to prevent shoulder injuries.

The contamination of water bodies by pesticide residues through direct flow, leaching and other methods has motivated the development of analytical methods for the determination of these compounds in water. A vortex-assisted liquid-liquid microextraction method followed by gas chromatography coupled to mass spectrometry for the determination of anilazine, linuron, prothiofos, and tebuconazole residues in water samples from the culture and processing of potatoes (Solanum tuberosum L.) was optimized. The complete factorial design and the central rotational compound design combined with the desirability function were used to evaluate and optimize the parameters of the method. The optimized conditions for extracting the pesticides were as follows: 316 µL of toluene, no sodium chloride addition, and a stirring time of 187 s. The method presented an enrichment factor of 142.4 times and good linearity, precision and accuracy, with limits of detection (LOD) of 0.005 - 0.007 mg L-1 and limits of quantification (LOQ) of 0.016 - 0.022 mg L-1. The co-extractives of the wastewater samples caused the suppression of the chromatographic response of linuron and prothiofos by 7.82 and 27.63%, respectively. The analyte concentrations in the wastewater samples from the industrial shing process, manual potato washing, and dam water were either lower than the LODs of the method or were absent.

Abstract Background Handrim wheelchair propulsion is often assessed in the laboratory on treadmills (TM) or ergometers (WE), under the assumption that they relate to regular overground (OG) propulsion. However, little is known about the agreement of data obtained from TM, WE, and OG propulsion under standardized conditions. The current study aimed to standardize velocity and power output among these three modalities to consequently compare obtained physiological and biomechanical outcome parameters. Methods Seventeen able-bodied participants performed two submaximal practice sessions before taking part in a measurement session consisting of 3 × 4 min of submaximal wheelchair propulsion in each of the different modalities. Power output and speed for TM and WE propulsion were matched with OG propulsion, making them (mechanically) as equal as possible. Physiological data and propulsion kinetics were recorded with a spirometer and a 3D measurement wheel, respectively. Results Agreement among conditions was moderate to good for most outcome variables. However, heart rate was significantly higher in OG propulsion than in the TM condition. Push time and contact angle were smaller and fraction of effective force was higher on the WE when compared to OG/TM propulsion. Participants used a larger cycle time and more negative work per cycle in the OG condition. A continuous analysis using statistical parametric mapping showed a lower torque profile in the start of the push phase for TM propulsion versus OG/WE propulsion. Total force was higher during the start of the push phase for the OG conditions when compared to TM/WE propulsion. Conclusions Physiological and biomechanical outcomes in general are similar, but possible differences between modalities exist, even after controlling for power output using conventional techniques. Further efforts towards increasing the ecological validity of lab-based equipment is advised and the possible impact of these differences -if at all- in (clinical) practice should be evaluated.

Abstract Background The impact of anemia treatment with erythropoietin stimulating agents (ESA) on health-related quality of life (HRQOL) in chronic kidney disease (CKD) patients is controversial, particularly regarding optimal hemoglobin (Hb) target ranges. Methods We conducted a systematic review and meta-analysis of observational studies and randomized controlled trials (RCT) with ESA to estimate the effect of different achieved Hb values on physical HRQOL and functionality. We searched PubMed, EMBASE, CENTRAL, PEDro, PsycINFO and Web of Science databases, until May 2020. Two authors independently extracted data from studies. We included observational and RCTs that enrolled CKD patients undergoing anemia treatment with ESA with different achieved Hb levels among groups. We excluded studies with achieved Hb 11.5 g/dL. We analyzed the standardized mean difference (SMD) between groups for physical HRQOL. Results Among 8496 studies, fifteen RCTs and five observational studies were included for the systematic review. We performed the meta-analysis in a subset of eleven eligible RCTs. For physical role and physical function, SMDs were 0.0875 [95% CI: − 0.0025 – 0.178] and 0.08 [95% CI: − 0.03 – 0.19], respectively. For fatigue, SMD was 0.16 [95% CI: 0.09–0.24]. Subgroup analysis showed that trials with greater achieved Hb had greater pooled effects sizes — 0.21 [95% CI: 0.07–0.36] for Hb > 13 g/dL vs. 0.09 [95% CI: 0.02–0.16] for Hb 11.5–13 g/dL. Proportion of older and long-term diabetic patients across studies were associated with lower effect sizes. Conclusion Achieved hemoglobin higher than currently recommended targets may be associated with small but potentially clinically significant improvement in fatigue, but not in physical role or physical function. Younger and non-diabetic patients may experience more pronounced benefits of higher Hb levels after treatment with ESAs.

ABSTRACT Due to a number of factors involving the thermal environment of a broiler cutting installation and its interaction with the physiological and productive responses of birds, artificial intelligence has been shown to be an interesting methodology to assist in the decision-making process. For this reason, the main aim of this work was to develop an artificial neural network (ANN) to predict feed conversion (FC), water consumption (Cwater), and cloacal temperature (tclo) of broilers submitted to different air dry-bulb temperatures (24, 27, 30, and 33°C) and durations (1, 2, 3, and 4 days) of thermal stress in the second week of the production cycle. Relative humidity and wind speed were fixed at 60% and 0.2 ms−1, respectively. The experimental data were used for the development of an ANN with supervised training using the Levenberg-Marquardt backpropagation algorithm. The ANN consisted of three input layers one hidden, and three output with sigmoidal tangent transfer functions with values between −1 and 1. The developed ANN has adequate predictive capacity, with coefficients of determination (R2) for tclo, FC, and Cwater of 0.79, 0.87, and 0.97, respectively. In this way, the proposed ANN can be used as a support for decision-making to trigger poultry heating systems for broiler breeding.

Abstract Background Originally, the cranks of a handcycle were mounted with a 180° phase shift (asynchronous). However, as handcycling became more popular, the crank mode switched to a parallel mounting (synchronous) over the years. Differences between both modes have been investigated, however, not into great detail for propulsion technique or practice effects. Our aim is to compare both crank modes from a biomechanical and physiological perspective, hence considering force and power production as a cause of physiological outcome measures. This is done within a practice protocol, as it is expected that motor learning takes place in the early stages of handcycling in novices. Methods Twelve able-bodied male novices volunteered to take part. The experiment consisted of a pre-test, three practice sessions and a post-test, which was subsequently repeated for both crank modes in a counterbalanced manner. In each session the participants handcycled for 3 × 4 minutes on a leveled motorized treadmill at 1.94 m/s. Inbetween sessions were 2 days of rest. 3D forces, handlebar and crank angle were measured on the left hand side. Kinematic markers were placed on the handcycle to monitor the movement on the treadmill. Lastly, breath-by-breath spirometry combined with heart-rate were continuously measured. The effects of crank mode and practice-based learning were analyzed using a two way repeated measures ANOVA, with synchronous vs asynchronous and pre-test vs post-test as within-subject factors. Results In the pre-test, asynchronous handcycling was less efficient than synchronous handcycling in terms of physiological strain, force production and timing. At the post-test, the metabolic costs were comparable for both modes. The force production was, also after practice, more efficient in the synchronous mode. External power production, crank rotation velocity and the distance travelled back and forwards on the treadmill suggest that asynchronous handcycling is more constant throughout the cycle. Conclusions As the metabolic costs were reduced in the asynchronous mode, we would advise to include a practice period, when comparing both modes in scientific experiments. For handcycle users, we would currently advise a synchronous set-up for daily use, as the force production is more effective in the synchronous mode, even after practice.

Objectives Despite the many proven advantages of a physically active lifestyle in patient populations, prescription of exercise is currently not widely implemented in routine clinical practice. The aims of this study were twofold: (1) to assess perceptions of clinicians on the current practice of exercise is medicine (E=M) prescription in two Dutch university medical centres and (2) to determine their perceived barriers and facilitators for the implementation of E=M in routine clinical care in Dutch university medical centres.Design A mixed methodologies study, using both online questionnaires and semi-structured interviews.Setting Dutch university medical centres.Participants Clinicians working within the departments of medical oncology, orthopaedics and rehabilitation medicine of two university medical centres.Results Forty-five clinicians (response rate of 51%) completed the questionnaire, and 19 clinicians were interviewed. The results showed that even though clinicians had a positive attitude towards prescribing E=M, only a few reported to regularly prescribe E=M to their patients. The 52 identified facilitators and barriers for implementation of E=M were categorised into four main themes: (1) beliefs toward the implementation of E=M (eg, clinicians knowledge and skills, and social support), (2) factors related to the patient perspective (eg, patient priorities or motivation), (3) factors related to the referral options (eg, knowledge of and trust in local referral options) and (4) practical considerations when implementing E=M (eg, time constraints).Conclusions Our study showed that even though many clinicians have a positive attitude toward an active lifestyle, many are not prescribing E=M on a regular basis. In order for clinicians to effectively implement E=M, strategies should focus on increasing clinicians E=M referral skills, improving clinicians knowledge of E=M referral options and develop a support system to ensure that E=M is high on the priority list of clinicians.

This study aims to evaluate whether a test protocol with standardized and individualized resistance settings leads to valid wheelchair Wingate tests (WAnT) and graded exercise tests (GXT) in healthy novices. Twenty able-bodied individuals (10M/10F, age 23 ± 2 years, body mass 72 ± 11 kg) performed an isometric strength test, sprint test, WAnT and GXT on a wheelchair ergometer. Using a previously developed set of regression equations, individuals' isometric strength outcome was used to estimate the WAnT result (P30est), from which an effective individual WAnT resistance was derived. The subsequently measured WAnT outcome (P30meas) was used to estimate the GXT outcome (POpeakest) and to scale the individual GXT resistance steps. Estimated and measured outcomes were compared. The WAnT protocol was considered valid when maximal velocity did not exceed 3 m·s-1; the GXT protocol was considered valid when test duration was 8-12 min. P30est did not significantly differ from P30meas, while one participant did not have a valid WanT, as maximal velocity exceeded 3 m·s-1. POpeakest was 10% higher than POpeakmeas, and six participants did not reach a valid GXT: five participants had a test duration under 8 min and one participant over 12 min. The isometric strength test can be used to individually scale the WAnT protocol. The WAnT outcome scaled the protocol for the GXT less accurately, resulting in mostly shorter-than-desired test durations. In conclusion, the evaluated standardized and individualized test protocol was valid for the WAnT but less valid for the GXT among a group of novices. Before implementing the standardized individual test protocol on a broader scale, e.g. among paralympic athletes, it should be evaluated among different athletic wheelchair-dependent populations.

Type 1 diabetes (T1D) is a disease that arises due to complex immunogenetic mechanisms. Key cell-cell interactions involved in the pathogenesis of T1D are activation of autoreactive T cells by dendritic cells (DC), migration of T cells across endothelial cells (EC) lining capillary walls into the islets of Langerhans, interaction of T cells with macrophages in the islets, and killing of β-cells by autoreactive CD8+ T cells. Overall, pathogenic cell-cell interactions are likely regulated by the individual’s collection of genetic T1D-risk variants. To accurately model the role of genetics, it is essential to build systems to interrogate single candidate genes in isolation during the interactions of cells that are essential for disease development. However, obtaining single-donor matched cells relevant to T1D is a challenge. Sourcing these genetic variants from human induced pluripotent stem cells (iPSC) avoids this limitation. Herein, we have differentiated iPSC from one donor into DC, macrophages, EC, and β-cells. Additionally, we also engineered T cell avatars from the same donor to provide an in vitro platform to study genetic influences on these critical cellular interactions. This proof of concept demonstrates the ability to derive an isogenic system from a single donor to study these relevant cell-cell interactions. Our system constitutes an interdisciplinary approach with a controlled environment that provides a proof-of-concept for future studies to determine the role of disease alleles (e.g. IFIH1, PTPN22, SH2B3, TYK2) in regulating cell-cell interactions and cell-specific contributions to the pathogenesis of T1D.

Real-life daily handcycling requires combined propulsion and steering to control the front wheel. Today, the handcycle cranks are mostly mounted synchronously unlike the early handcycle generations. Alternatively, arm cycle ergometers do not require steering and the cranks are mostly positioned asynchronously. The current study aims to evaluate the effects of combining propulsion and steering requirements on synchronous and asynchronous submaximal handcycle ergometry. We hypothesize that asynchronous handcycling with steering results in the mechanically least efficient condition, due to compensation for unwanted rotations that are not seen in synchronous handcycling, regardless of steering. Sixteen able-bodied male novices volunteered in this lab-based experiment. The set-up consisted of a handcycle ergometer with 3D force sensors at each crank that also allows “natural” steering. Four submaximal steady-state (60 rpm, ~35 W) exercise conditions were presented in a counterbalanced order: synchronous with a fixed steering axis, synchronous with steering, asynchronous with a fixed axis and asynchronous with steering. All participants practiced 3 × 4 mins with 30 mins rest in between every condition. Finally, they did handcycle for 4 mins in each of the four conditions, interspaced with 10 mins rest, while metabolic outcomes, kinetics and kinematics of the ergometer were recorded. The additional steering component did not influence velocity, torque and power production during synchronous handcycling and therefore resulted in an equal metabolically efficient handcycling configuration compared to the fixed condition. Contrarily, asynchronous handcycling with steering requirements showed a reduced mechanical efficiency, as velocity around the steering axis increased and torque and power production were less effective. Based on the torque production around the crank and steering axes, neuromuscular compensation strategies seem necessary to prevent steering movements in the asynchronous mode. To practice or test real-life daily synchronous handcycling, a synchronous crank set-up of the ergometer is advised, as exercise performance in terms of mechanical efficiency, metabolic strain, and torque production is independent of steering requirements in that mode. Asynchronous handcycling or arm ergometry demands a different handcycle technique in terms of torque production and results in higher metabolic responses than synchronous handcycling, making it unsuitable for testing.

Abstract The European Reference Network for rare liver diseases (ERN RARE-LIVER) is a Europe-wide network of paediatric and adult hepatologists from expert centres in close collaboration with patient advocates from the various disease-areas covered in our ERN. The ERN is focused on providing more equitable care across Europe and creates a network of both medical specialists and patient experts in rare liver disease. This position paper summarizes the achievements of the first year and plots the route for the near future for ERN RARE-LIVER, as discussed during a strategy meeting that took place 27 and 28 February 2018 in Nijmegen, the Netherlands. ERN RARE-LIVER has established itself as a group with experts, hospitals and patients. One of the tools to improve communication is the clinical patient management system (CPMS) that allows access to expert consultation by European physicians confronted with a patient with rare liver disease. ERN RARE-LIVER will function as the platform to improve healthcare by initiating registries, foster research efforts and coordinate development of clinical guidelines in Europe.

Platelet aggregates generate contractile forces that contribute to their cohesion and adhesion. Here, Ting et al. develop a microfluidic device to measure contractile forces generated by platelet aggregates, and find it can detect the response of platelets to pharmacological agents and predict bleeding risk in trauma patients.

Ice-flow fields, including the driving stress, provide important information on the current state and evolution of Antarctic and Greenland ice-sheet dynamics. However, computation of flow fields from continent-scale DEMs requires the use of smoothing functions and scales, the choice of which can be ad hoc. This study evaluates smoothing functions and scales for robust calculations of driving stress from Antarctic DEMs. Our approach compares a variety of filters and scales for their capacity to minimize the residual between predicted and observed flow direction fields. We find that a spatially varying triangular filter with a width of 8–10 ice thicknesses provides the closest match between the observed and predicted flow direction fields. We use the predicted flow direction fields to highlight artefacts in observed Antarctic velocities, demonstrating that comparison of multiple observational data sets has utility for quality control of continent-scale data sets.

IntroductionEvaluation of the effect of human upper-body training regimens may benefit from knowledge of local energy expenditure in arm muscles. To that end, we developed a novel arm-crank ergometry platform for use in a clinical magnetic resonance (MR) scanner with 31P spectroscopy capability to study arm muscle energetics. Complementary datasets on heart-rate, whole-body oxygen consumption, proximal arm-muscle electrical activity and power output, were obtained in a mock-up scanner. The utility of the platform was tested by a preliminary study over 4 weeks of skill practice on the efficiency of execution of a dynamic arm-cranking task in healthy subjects.ResultsThe new platform successfully recorded the first ever in vivo31P MR spectra from the human biceps brachii (BB) muscle during dynamic exercise in five healthy subjects. Changes in BB energy- and pH balance varied considerably between individuals. Surface electromyography and mechanical force recordings revealed that individuals employed different arm muscle recruitment strategies, using either predominantly elbow flexor muscles (pull strategy; two subjects), elbow extensor muscles (push strategy; one subject) or a combination of both (two subjects). The magnitude of observed changes in BB energy- and pH balance during ACT execution correlated closely with each strategy. Skill practice improved muscle coordination but did not alter individual strategies. Mechanical efficiency on group level seemed to increase as a result of practice, but the outcomes generated by the new platform showed the additional caution necessary for the interpretation that total energy cost was actually reduced at the same workload.ConclusionThe presented platform integrates dynamic in vivo31P MRS recordings from proximal arm muscles with whole-body calorimetry, surface electromyography and biomechanical measurements. This new methodology enables evaluation of cyclic motor performance and outcomes of upper-body training regimens in healthy novices. It may be equally useful for investigations of exercise physiology in lower-limb impaired athletes and wheelchair users as well as frail patients including patients with debilitating muscle disease and the elderly.

Protein tyrosine phosphatase, non-receptor type 22 (PTPN22) regulates a panoply of leukocyte signaling pathways. A single nucleotide polymorphism (SNP) in PTPN22, rs2476601, is associated with increased risk of Type 1 Diabetes (T1D) and other autoimmune diseases. Over the past decade PTPN22 has been studied intensely in T cell receptor (TCR) and B cell receptor (BCR) signaling. However, the effect of the minor allele on PTPN22 function in TCR signaling is controversial with some reports concluding it has enhanced function and blunts TCR signaling and others reporting it has reduced function and increases TCR signaling. More recently, the core function of PTPN22 as well as functional derangements imparted by the autoimmunity-associated variant allele of PTPN22 have been examined in monocytes, macrophages, dendritic cells, and neutrophils. In this review we will discuss the known functions of PTPN22 in human cells, and we will elaborate on how autoimmunity-associated variants influence these functions across the panoply of immune cells that express PTPN22. Further, we consider currently unresolved questions that require clarification on the role of PTPN22 in immune cell function.

BackgroundThe rising prevalence of modifiable lifestyle-related risk factors (e.g. overweight and physical inactivity) suggests the need for effective and safe preoperative interventions to improve outcomes after cardiac surgery. This retrospective study explored potential short-term postoperative benefits and unintended consequences of a multidisciplinary prehabilitation program regarding in-hospital complications.MethodsData on patients who underwent elective cardiac surgery between January 2014 and April 2017 were analyzed retrospectively. Pearson's chi-squared tests were used to compare patients who followed prehabilitation (three times per week, at a minimum of three weeks) during the waiting period with patients who received no prehabilitation. Sensitivity analyses were performed using propensity-score matching, in which the propensity score was based on the baseline variables that affected the outcomes.ResultsOf 1201 patients referred for elective cardiac surgery, 880 patients met the inclusion criteria, of whom 91 followed prehabilitation (53.8% ≥ 65 years, 78.0% male, median Euroscore II 1.3, IQR, 0.9-2.7) and 789 received no prehabilitation (60.7% ≥ 65 years, 69.6% male, median Euroscore II 1.6, IQR, 1.0-2.8). The incidence of atrial fibrillation (AF) was significantly lower in the prehabilitation group compared to the unmatched and matched standard care group (resp. 14.3% vs. 23.8%, P = 0.040 and 14.3% vs. 25.3%, P = 0.030). For the other complications, no between-group differences were found.ConclusionsPrehabilitation might be beneficial to prevent postoperative AF. Patients participated safely in prehabilitation and were not at higher risk for postoperative complications. However, well-powered randomized controlled trials are needed to confirm and deepen these results.

Risk management of electric power transmission lines requires knowledge from different areas such as the environment, land, investors, regulations, and engineering. Despite the widespread availability of databases for most of those areas, integrating them into a single database or model is a challenging problem. Instead, in this paper, we propose a novel method to calculate risk probabilities on the implementation of transmission lines based on unstructured text from a single source. It uses the Brazilian National Electric Energy Agency’s (ANEEL) weekly reports, which contain decisions about the electrical grid comprising most of the aforementioned areas. Since the data are unstructured (text), we employed NLP techniques such as stemming and tokenization to identify keywords related to common causes of risks provided by an expert group on energy transmission. Then, we used models to estimate the probability of each risk. This method differs from previous works, which were based on structured data (numerical or categorical) from single or multiple sources. Our results show that we were able to extract relevant keywords from the ANEEL reports that enabled our proposed method to estimate the probability of 97 risks out of 233 listed by an expert.

This article presents a novel method for predicting the sugarcane harvesting date and productivity using a three-band imaging radar. Taking advantage of working with a multi-band radar, this system was employed to estimate the above-ground biomass (AGB), achieving a root-mean-square error (RMSE) of 2 kg m−2 in sugarcane crops, which is an unprecedented result compared with other works based on the Synthetic Aperture Radar (SAR) system. By correlating the field measurements of the ripening index (RI) with the AGB measurements by radar, an indirect estimate of the RI by the radar is obtained. It is observed that the AGB reaches its maximum approximately 280 days after planting and the maximum RI, which defines the harvesting date, approximately 360 days after planting for the species IACSP97-4039. Starting from an AGB map collected by the radar, it is then possible to predict the harvesting date and the corresponding productivity with competitive average errors of 8 days and 10.7%, respectively, with three months in advance, whereas typical methods employed on a test site achieve an average error of 30 days with three months in advance. To the best of our knowledge, it is the first time that a multi-band radar is employed for productivity prediction in sugarcane crops.

Infection with human immunodeficiency virus 1 (HIV-1) remains incurable because long-lived, latently-infected cells persist during prolonged antiretroviral therapy. Attempts to pharmacologically reactivate and purge the latent reservoir with latency reactivating agents (LRAs) such as protein kinase C (PKC) agonists (e.g. ingenol A) or histone deacetylase (HDAC) inhibitors (e.g. SAHA) have shown promising but incomplete efficacy. Using the J-Lat T cell model of HIV latency, we found that the plant-derived compound harmine enhanced the efficacy of existing PKC agonist LRAs in reactivating latently-infected cells. Treatment with harmine increased not only the number of reactivated cells but also increased HIV transcription and protein expression on a per-cell basis. Importantly, we observed a synergistic effect when harmine was used in combination with ingenol A and the HDAC inhibitor SAHA. An investigation into the mechanism revealed that harmine, when used with LRAs, increased the activity of NFκB, MAPK p38, and ERK1/2. Harmine treatment also resulted in reduced expression of HEXIM1, a negative regulator of transcriptional elongation. Thus, harmine enhanced the effects of LRAs by increasing the availability of transcription factors needed for HIV reactivation and promoting transcriptional elongation. Combination therapies with harmine and LRAs could benefit patients by achieving deeper reactivation of the latent pool of HIV provirus.

The aim of this work was to study the effect of a high sodium (HS) diet on blood pressure and renal function in male adult rats that have been treated with a dual Endothelin receptor antagonist (ERA) during their early postnatal period (day 1 to 20 of life). Male Sprague-Dawley rats were divided in four groups: CNS: control rats with normosodic diet; ERANS: ERA-treated rats with normosodic diet; CHS: control rats with high sodium diet; ERAHS: ERA-treated rats with HS diet. Systolic blood pressure (SBP) was recorded before and after the diet and 24-hour metabolic cage studies were performed. AQP2 and α-ENac expressions were measured by western blot and real time PCR in the renal medulla. Vasopressin (AVP) pathway was evaluated by measuring V2 receptor and adenylyl cyclase 6 (AC6) expression and cAMP production in the renal medulla. Pre-pro ET-1mRNA was also evaluated in the renal medulla. Only rats that had been treated with an ERA during their postnatal period increased their SBP after consumption of a HS diet, showing an impaired capacity to excrete sodium and water, i.e. developing salt sensitivity. This salt sensitivity would be mediated by an increase in renomedullary expression and activity of AQP2 and α-ENaC as a consequence of increased AC6 expression and cAMP production and/or a decreased ET-1 production in the renal medulla. The knowledge of the molecular mechanisms underlying the perinatal programming of salt sensitive hypertension will allow the development of reprogramming strategies in order to avoid this pathology.

Background The co-inoculation of soybean with Bradyrhizobium and other plant growth-promoting rhizobacteria (PGPR) is considered a promising technology. However, there has been little quantitative analysis of the effects of this technique on yield variables. In this context, the present study aiming to provide a quantification of the effects of the co-inoculation of Bradyrhizobium and PGPR on the soybean crop using a meta-analysis approach. Methods A total of 42 published articles were examined, all of which considered the effects of co-inoculation of PGPR and Bradyrhizobium on the number of nodules, nodule biomass, root biomass, shoot biomass, shoot nitrogen content, and grain yield of soybean. We also determined whether the genus of the PGPR used as co-inoculant, as well as the experimental conditions, altered the effect size of the PGPR. Results The co-inoculation technology resulted in a significant increase in nodule number (11.40%), nodule biomass (6.47%), root biomass (12.84%), and shoot biomass (6.53%). Despite these positive results, no significant increase was observed in shoot nitrogen content and grain yield. The response of the co-inoculation varied according to the PGPR genus used as co-inoculant, as well as with the experimental conditions. In general, the genera Azospirillum, Bacillus, and Pseudomonas were more effective than Serratia. Overall, the observed increments were more pronounced under pot than that of field conditions. Collectively, this study summarize that co-inoculation improves plant development and increases nodulation, which may be important in overcoming nutritional limitations and potential stresses during the plant growth cycle, even though significant increases in grain yield have not been evidenced by this data meta-analysis.

ABSTRACT This study aimed to compare fuzzy systems with different configurations to predict the surface temperature (ts) of broiler chickens subjected to different intensities and durations of thermal challenges in the second week of life. Data on the ts of broiler chickens aged 8 to 11 days were acquired by infrared thermography and subjected to combinations of four dry-bulb temperatures (tdb) (24, 27, 30, and 33 °C) and four durations of thermal challenges (DTC) (1, 2, 3, or 4 days). The input variables of the fuzzy systems were tdb and DTC, and the output variable was ts. The Mamdani inference method involving five defuzzification methods [center of gravity (centroid), bisector of the area (bisector), largest of maximum (lom), middle of maximum (mom), and smallest of maximum (som)], and Sugeno inference with two defuzzification methods [weighted average (wtaver) and weighted sum (wtsum)] were evaluated. For both inference methods, triangular and Gaussian pertinence functions were tested for input and output variables, except for Sugeno inference, which used singletons functions as output variables. While developing fuzzy systems, different configurations must be compared, and the system with smaller simulation errors should be selected.

ABSTRACT Physiological parameters such as respiratory frequency and rectal temperature stand out as indicators for heat stress in pigs, however, requiring time and labor for measurements. The possibility of using infrared thermography associated with prediction systems of these physiological variables can help in decision making, allowing greater welfare and productivity of the animals. With this objective, an experiment was carried out with growing pigs submitted to acute and chronic heat stress, working with a thermoneutrality temperature (22° C) and heat stress (34° C). The results were used for the development of a fuzzy model using as input variables: air dry bulb temperature (°C), average surface temperature (°C) and, as output variables: respiratory frequency (movements/minute) and rectal temperature (°C). The method of inference used was the one of Mamdani having been elaborated six rules and the defuzzification technique used was the one of the Center of Gravity. In the obtained results on simulation model when compared with experimental data was evidenced satisfactory efficiency in respiratory frequency determination and the rectal temperature, in which the R2 values calculated were respectively 0.997 and 0.951 for acute stress and 0.993 and 0.964 for chronic heat stress.